The PSA Screening Debate and Active Surveillance

"There is a lot of confusion because there are so many opinions."
Carter is also the author of The Whole Life Prostate Book.

When the American Urological Association convened a panel to help men and their doctors make decisions about prostate cancer screening, it chose to lead it the Hopkins urologist whose ongoing, pioneering work on PSA screening has shaped much of the debate: H. Ballentine Carter, M.D.

"There is a lot of confusion because there are so many opinions," says Carter. "Views on PSA -based screening for prostate cancer vary widely – from a 'one-size-fits-all' approach that recommends starting when men turn 40, to a recommendation not to use the test at all." Opinions on treating prostate cancer are no less disparate, ranging from "treating all cancers to treating hardly any of them," Carter adds. The panel's interpretation of the evidence was that men between the ages of 55 and 69 are those most likely to benefit from screening, and that a man should only be screened after hearing about both the benefits and harms. "The major harm of screening is that a substantial minority of men, depending on age, will be diagnosed with a cancer that would never have caused harm," says Carter. "If treated, these men risk the side effects of treatment without the benefit in terms of extending life."

" The major harm of screening is

that a substantial minority of men,

depending on age, will be diagnosed with

a cancer that would never have caused harm.

But who can safely avoid treatment?"

The other approach is not to treat every man diagnosed with prostate cancer. "But who can safely avoid treatment?" Carter began working to answer this question 16 years ago when he developed the Active Surveillance Program for prostate cancer at Hopkins. Now the careful collection of data from men in the program is paying off: In 2012 and 2013, a number of studies based on the Johns Hopkins experience with surveillance and surgery were carried out to learn more about the safety of surveillance. The big question these studies sought to answer: Which men can avoid treatment without compromising their chance of a cure?

Investigators from Hopkins, the Fred Hutchinson Cancer Center, and the University of California-San Francisco (UCSF) teamed up to compare the outcomes of men enrolled in the Active Surveillance Program at Hopkins with those of men who underwent surgery immediately at Hopkins and UCSF after their cancer was diagnosed. "Since no trial has directly compared surgery versus surveillance, the investigators used a simulation model to project the likelihood of prostate cancer death in the two groups," Carter reports. The scientists projected that 2.8 percent of men on active surveillance and 1.6 percent of the men who underwent immediate radical prostatectomy would die of their disease in 20 years. They estimated that the average increase in life expectancy associated with immediate radical prostatectomy was 1.8 months, and that men on active surveillance would remain free of treatment for an additional 6.4 years as compared to men who had immediate treatment. "These findings suggest that men enrolled in the Johns Hopkins Active Surveillance Program are at low risk of losing a window of opportunity for cure if they are carefully monitored," Carter says.

However, men who qualify for the Active Surveillance Program are somewhat of an exclusive group; most men who are diagnosed with prostate cancer do not fit the program's stringent criteria. To be enrolled in the Active Surveillance Program at Hopkins, a man must have low-grade and small-volume disease – cancer categorized as "very low risk"

Very Low Risk

You are considered to have very low-risk prostate cancer if:

Your biopsy has a Gleason score of 6,

2 cores or fewer are found to contain cancer,

Cancer makes up half or less of any core that contains cancer,

PSA divided by the prostate volume is 0.15 or less, and

Cancer is not palpable on a digital rectal examination

Low Risk

You are considered to have very low-risk prostate cancer if:

Your PSA is below 10 ng/ml

Your biopsy has a Gleason score of 6

Cancer is not palpable or is minimally palpable on a digital rectal
examination

What about men with low-risk cancer? These men have low-grade, but not low-volume cancers. Recently, Jeff Tosoian, M.D., now a urology resident, studied men with very low-risk and low-risk disease who underwent surgery at Hopkins. "Since they underwent surgery, it was possible to compare the extent of cancer in the two groups," says Carter. After evaluating the extent of cancer among 7,333 men classified as low-risk, and 153 men diagnosed with very low-risk disease, Tosoian concluded that men with low-risk disease were approximately two times more likely than very low-risk men to have a cancer that turned out to be of higher grade and/ or to have spread beyond the prostate gland. "This finding suggests that surveillance may be more risky in the presence of low-risk versus very low-risk disease, especially in younger men," says Carter. "Men who can expect to live at least 20 more years who have low-risk disease may rather accept the risks of treatment than take the chance that their cancer will cause harm later, especially if they are otherwise healthy. Men with very low-risk disease can take comfort that their disease can safely be managed by surveillance."

An interesting note: Some men enrolled in active surveillance are found to have a higher grade of cancer in a follow-up biopsy months or years down the road. Does this mean that the low-grade cancer somehow evolved to become a higher-grade cancer? Or did the high-grade cancer just develop by itself? "This is an important question," says Carter, "given the enthusiasm for therapies that target low-grade cancers without destroying the whole gland," treatment known as focal therapy. "In one of our patients on active surveillance, a particularly aggressive cancer was found 16 years after the man was diagnosed with low-grade cancer." Fortunately, the Active Surveillance Program saves the tissue from serial biopsies. Scientist Michael Haffner, M.D., made genetic "fingerprints" of the cancer samples and found that the genetic profile of the aggressive disease was different from that of the low-grade cancer. "This suggests that the higher-grade, aggressive cancer did not arise from the low-grade cancer," says Carter. "It is not known whether this is a unique or a common situation, but in the future we may answer this question using tissue samples stored as part of our Active